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Q1LZ53 (DNM3A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 67. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA (cytosine-5)-methyltransferase 3A

Short name=Dnmt3a
EC=2.1.1.37
Gene names
Name:Dnmt3a
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length908 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Can actively repress transcription through the recruitment of HDAC activity By similarity.

Catalytic activity

S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.

Enzyme regulation

Activated by binding to the regulatory factor DNMT3L By similarity.

Subunit structure

Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) By similarity. Interacts with DNMT1 and DNMT3B. Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain By similarity. Interacts with the PRC2/EED-EZH2 complex By similarity. Interacts with UBC9, PIAS1 and PIAS2 By similarity. Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4). Interacts with UHRF1 By similarity.

Subcellular location

Nucleus By similarity. Cytoplasm By similarity.

Domain

The PWWP domain is essential for targeting to pericentric heterochromatin.

Post-translational modification

Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription By similarity.

Sequence similarities

Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.

Contains 1 ADD domain.

Contains 1 GATA-type zinc finger.

Contains 1 PHD-type zinc finger.

Contains 1 PWWP domain.

Contains 1 SAM-dependent MTase C5-type domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative promoter usage
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
S-adenosyl-L-methionine
Zinc
   Molecular functionChromatin regulator
Methyltransferase
Repressor
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processC-5 methylation of cytosine

Inferred from direct assay PubMed 11844796. Source: GOC

DNA methylation

Inferred from sequence or structural similarity PubMed 12138111. Source: UniProtKB

DNA methylation involved in embryo development

Inferred from electronic annotation. Source: Ensembl

DNA methylation involved in gamete generation

Inferred from electronic annotation. Source: Ensembl

DNA methylation on cytosine within a CG sequence

Inferred from direct assay PubMed 11844796. Source: RGD

S-adenosylhomocysteine metabolic process

Inferred from direct assay PubMed 11844796. Source: RGD

S-adenosylmethioninamine metabolic process

Inferred from direct assay PubMed 11844796. Source: RGD

cellular response to amino acid stimulus

Inferred from electronic annotation. Source: Ensembl

hypermethylation of CpG island

Inferred from electronic annotation. Source: Ensembl

methylation-dependent chromatin silencing

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

regulation of gene expression by genetic imprinting

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentchromosome, centromeric region

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from sequence or structural similarity PubMed 12138111. Source: UniProtKB

euchromatin

Inferred from sequence or structural similarity PubMed 12138111. Source: UniProtKB

nuclear heterochromatin

Inferred from electronic annotation. Source: Ensembl

nuclear matrix

Inferred from sequence or structural similarity PubMed 12138111. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity PubMed 12138111. Source: UniProtKB

   Molecular_functionDNA (cytosine-5-)-methyltransferase activity

Inferred from sequence or structural similarity PubMed 12138111. Source: UniProtKB

DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates

Inferred from direct assay PubMed 11844796. Source: RGD

DNA binding

Inferred from sequence or structural similarity PubMed 12138111. Source: UniProtKB

chromatin binding

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

unmethylated CpG binding

Inferred from direct assay PubMed 11844796. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage. [Align] [Select]
Isoform 1 (identifier: Q1LZ53-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q1LZ53-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-219: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 908908DNA (cytosine-5)-methyltransferase 3A
PRO_0000313030

Regions

Domain257 – 31559PWWP
Domain478 – 610133ADD
Domain630 – 908279SAM-dependent MTase C5-type
Zinc finger489 – 51931GATA-type; atypical
Zinc finger530 – 58657PHD-type; atypical
Region195 – 399205Interaction with DNMT1 and DNMT3B By similarity
Region490 – 58293Interaction with the PRC2/EED-EZH2 complex By similarity
Region637 – 6415S-adenosyl-L-methionine binding By similarity
Region682 – 6843S-adenosyl-L-methionine binding By similarity
Region887 – 8893S-adenosyl-L-methionine binding By similarity
Compositional bias479 – 52749Cys-rich

Sites

Active site7061 By similarity
Binding site6601S-adenosyl-L-methionine By similarity

Amino acid modifications

Modified residue1021Phosphoserine By similarity
Modified residue2391Phosphoserine By similarity
Modified residue2511Phosphoserine By similarity
Modified residue2571Phosphothreonine By similarity

Natural variations

Alternative sequence1 – 219219Missing in isoform 2.
VSP_029986

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 30, 2006. Version 1.
Checksum: 6CCE9EB4E9CEB409

FASTA908101,669
        10         20         30         40         50         60 
MPSSGPGDTS ISSLEREDDR KEGEEQEENR GKEERQEPSA TARKVGRPGR KRKHPPVESS 

        70         80         90        100        110        120 
DTPKDPAVTT KSQPTAQDSG PSDLLPNGDL EKRSEPQPEE GSPAAGQKGG APAEGEGTET 

       130        140        150        160        170        180 
PPEASRAVEN GCCVTKEGRG ASAGEGKEQK QTNIESMKME GSRGRLRGGL GWESSLRQRP 

       190        200        210        220        230        240 
MPRLTFQAGD PYYISKRKRD EWLARWKREA EKKAKVIAVM NAVEESQASG ESQKVEEASP 

       250        260        270        280        290        300 
PAVQQPTDPA SPTVATTPEP VGADAGDKNA TKAADDEPEY EDGRGFGIGE LVWGKLRGFS 

       310        320        330        340        350        360 
WWPGRIVSWW MTGRSRAAEG TRWVMWFGDG KFSVVCVEKL MPLSSFCSAF HQATYNKQPM 

       370        380        390        400        410        420 
YRKAIYEVLQ VASSRAGKLF PACHDSDESD TGKAVEVQNK QMIEWALGGF QPSGPKGLEP 

       430        440        450        460        470        480 
PEEEKNPYKE VYTDMWVEPE AAAYAPPPPA KKPRKSTTEK PKVKEIIDER TRERLVYEVR 

       490        500        510        520        530        540 
QKCRNIEDIC ISCGSLNVTL EHPLFIGGMC QNCKNCFLEC AYQYDDDGYQ SYCTICCGGR 

       550        560        570        580        590        600 
EVLMCGNNNC CRCFCVECVD LLVGPGAAQA AIKEDPWNCY MCGHKGTYGL LRRREDWPSR 

       610        620        630        640        650        660 
LQMFFANNHD QEFDPPKVYP PVPAEKRKPI RVLSLFDGIA TGLLVLKDLG IQVDRYIASE 

       670        680        690        700        710        720 
VCEDSITVGM VRHQGKIMYV GDVRSVTQKH IQEWGPFDLV IGGSPCNDLS IVNPARKGLY 

       730        740        750        760        770        780 
EGTGRLFFEF YRLLHDARPK EGDDRPFFWL FENVVAMGVS DKRDISRFLE SNPVMIDAKE 

       790        800        810        820        830        840 
VSAAHRARYF WGNLPGMNRP LASTVNDKLE LQECLEHGRI AKFSKVRTIT TRSNSIKQGK 

       850        860        870        880        890        900 
DQHFPVFMNE KEDILWCTEM ERVFGFPVHY TDVSNMSRLA RQRLLGRSWS VPVIRHLFAP 


LKEYFACV 

« Hide

Isoform 2 [UniParc].

Checksum: 1C75674CFC1C97BE
Show »

FASTA68977,825

References

[1]"Identification of 11 pseudogenes in the DNA methyltransferase gene family in rodents and humans and implications for the functional loci."
Lees-Murdock D.J., McLoughlin G.A., McDaid J.R., Quinn L.M., O'Doherty A., Hiripi L., Hack C.J., Walsh C.P.
Genomics 84:193-204(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BN000395 mRNA. Translation: CAE52317.1.
BN000396 mRNA. Translation: CAE52318.1.
RefSeqNP_001003957.1. NM_001003957.1.
NP_001003958.1. NM_001003958.1.
UniGeneRn.92659.

3D structure databases

ProteinModelPortalQ1LZ53.
SMRQ1LZ53. Positions 279-420, 623-908.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ1LZ53.

Proteomic databases

PaxDbQ1LZ53.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000047210; ENSRNOP00000046524; ENSRNOG00000026649. [Q1LZ53-1]
GeneID444984.
KEGGrno:444984.

Organism-specific databases

CTD1788.
RGD1303336. Dnmt3a.

Phylogenomic databases

eggNOGNOG70699.
GeneTreeENSGT00390000008341.
HOGENOMHOG000230875.
HOVERGENHBG051381.
InParanoidQ1LZ53.
KOK17398.
OMAFVGGMCQ.
OrthoDBEOG7MWGW6.
PhylomeDBQ1LZ53.
TreeFamTF329039.

Gene expression databases

GenevestigatorQ1LZ53.

Family and domain databases

InterProIPR025766. ADD.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR025811. C5_MeTrfase_3.
IPR000313. PWWP_dom.
[Graphical view]
PfamPF00145. DNA_methylase. 1 hit.
PF00855. PWWP. 1 hit.
[Graphical view]
SMARTSM00293. PWWP. 1 hit.
[Graphical view]
PROSITEPS51533. ADD. 1 hit.
PS00094. C5_MTASE_1. 1 hit.
PS50812. PWWP. 1 hit.
PS51679. SAM_MT_C5. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio697058.

Entry information

Entry nameDNM3A_RAT
AccessionPrimary (citable) accession number: Q1LZ53
Secondary accession number(s): Q1LZ52
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: May 30, 2006
Last modified: April 16, 2014
This is version 67 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families